Methods and devices usable in eye surgery

ABSTRACT

A device ( 10 ) for preventing leakage of gas from a lens capsule of an eye, to which a capsulorhexis has been made, during manipulations performed inside the lens capsule. It includes a tube ( 12 ) having at least one lumen ( 14 ). The tube is provided with at least one barrier member ( 16; 17 ) such that gas that has been introduced into the lens capsule is prevented to escape therefrom. It also relates to a method of eye surgery. It includes making an incision to gain access to the interior of an eye. Making a capsulorhexis in the lens capsule. Removing the lens from the lens capsule of an eye. Sealing the capsulorhexis with a sealing device, to provide gas leakage proof sealing. Expanding the lens capsule with a gas. Performing a desired operation inside the expanded lens capsule.

The present invention relates to eye surgery, and in particular to amethod and devices for allowing and facilitating efficient removal orinactivation of lens epithelial cells for the purpose of preventingCapsular Opacification.

BACKGROUND OF THE INVENTION

The crystalline lens of the human eye is located in the posteriorchamber between the posterior iris surface and the vitreous body. It isa biconvex transparent tissue without nerves and blood vessels, weighingapproximately 0.2 g. The lens is enveloped in a capsule, astructureless, transparent and elastic membrane bag. Approximately 80zonular fibers, extending between the capsule and the ciliary body,suspend the lens. The inside of the lens capsule consists of lensepithelial cells and lens fibers. The lens epithelial cells form amonolayer underlying the capsule from the anterior pole to the equatorof the lens. These cells continue to undergo cell mitosis throughoutlife in the area located between the anterior pole and the lens equator.The lens epithelial cells that underwent cell mitosis gradually movetoward the lens equator and differentiate into lens fibers. These cellsmake up the rest of the lens. New layers of fiber cells are constantlyformed on top of those previously formed. The older fiber cells becomedenser and during the 3rd decade of life a hard nucleus is formed in themiddle of the human lens, consisting of old dehydrated fiber cells.

A cataract is defined as every form of opacity in the lens or itscapsule; the lens becomes cloudy, resulting in a loss of visual ability.A cataract is a painless phenomenon, but decreases the quality of lifeif the lens is not surgically extracted and replaced by an artificiallens.

When the lens is surgically extracted, an incision is made in theanterior part of the eye, i.e., the cornea or the sclera. Then, aviscoelastic material is usually introduced into the anterior chamber tomaintain the anterior chamber depth during surgery. An opening is madein the lens capsule by a procedure called capsulorhexis.

Following capsulorhexis, the lens is removed according to one of twoprinciples: extracapsular cataract extraction (ECCE)—the cataractouslens is squeezed out through an opening in the anterior lens capsule andthen removed through a 10-12 mm-corneal incision, orphacoemulsification—the cataractous lens is dissolved with a specialinstrument, phaco-probe, by high frequency sonification and rinsed outthrough a 3-4 mm corneal incision.

Remaining parts of the lens, i.e. lens fibers and lens epithelial cells,are then removed using an irrigation and aspiration device. Aftercomplete removal of the lens, the lens capsule is filled with aviscoelastic material and an artificial lens is implanted into it.Alternatively, a lens can be molded inside the lens capsule, asdisclosed in PCT/EP99/07780. Thereby a cross-linkable polymer isinjected into a lens capsule, and the lens is formed in situ. Anothermethod for the same purpose but employing other materials is disclosedin PCT/EP01/04010.

Dyeing of the anterior lens capsule has been used to facilitatecapsulorhexis in advanced/white cataract, to enhance critical stepsduring phacoemulsification and to perform capsulorhexis of the posteriorlens capsule. Earlier studies have evaluated dyes, such as crystalviolet, fluorescein, and indocyanine green, for dyeing the anterior lenscapsule. Some dyes are applied by injection under the anterior surfaceof the capsule. Others are applied by a certain technique in which theanterior chamber is filled by gas, and the dye is applied on top of theanterior surface of the capsule. After a while, the dye is washed awayby irrigation/aspiration and the anterior chamber is filled by aviscoelastic solution followed by capsulorhexis.

After cataract surgery, the most common postoperative complication isposterior capsule opacification (PCO) which has the clinical andeconomic significance to be considered as an important public healthproblem. Studies report that the incidence of PCO is ranging from 20% to40% after approximately 4 years after surgery. Migration andproliferation of remaining lens epithelial cells is the main cause ofPCO. These cells grow from the peripheral parts of the capsule onto theposterior capsule and continue toward the axial region. Impaired visualacuity is the result caused by cell migration, proliferation andaggregation, the production of extracellular matrix, fibrosis andwrinkling of the lens capsule.

In the current clinical standard, patients who develop PCO are treatedsymptomatically by YAG laser capsulotomy. In this procedure a YAG laserdisrupts the opacified lens capsule and the visual axis is cleared.However, YAG laser capsulotomy exposes patients to the risk ofcomplications that can lead to severe visual impairment or loss ofvision, such as retinal detachment, pupillary block glaucoma and cystoidmacular edema. Other complications associated with YAG laser capsulotomyinclude damage to implanted intraocular lenses resulting in glare andphotophobia, dislocation of intraocular lenses, iritis, vitritis,corneal edema, iris damage and rupture of the anterior hyaloid.

From an economic point of view, symptomatic treatment of PCO is rankedone of the highest of the medical costs in the U.S.A. Thus, developmentof a procedure to prevent PCO reduces the medical costs related to YAGlaser capsulotomy, including the costs for the treatment, itscomplications, and YAG laser equipment. Accordingly, there is a greatneed for PCO prophylaxis.

Mechanical and pharmaceutical methods for PCO prophylaxis by removing ordestroying residual lens epithelial cells have been developed. However,none of them has been proved to be practical, effective, and safe enoughfor routine clinical practice.

Capsular polishing, aspiration of residual lens epithelial cells,ultrasound combined with aspiration, cryocoagulation, and osmolysis areexamples of methods that have been developed and shown to remove ordestroy remaining lens epithelial cells, but none of these methods havebeen proven to be efficient in PCO prophylaxis.

The design of the artificial intraocular lenses (IOL), such as theshape, size and materials of the IOL implanted during cataract surgeryhas also been shown to affect the development of PCO. It has been shownthat a sharp bend in the capsule, created by a capsule tension ring oran IOL with sharp optic edges, may induce contact inhibition of lensepithelial cell migration on the capsule.

Various anti-metabolites such as doxorubicin, methotrexate, mitomycin,daunomycin/daunorubicin, 5 fluorouracil, colchicines, and taxol areeffective in inhibiting lens epithelial cells proliferation in vitro.However, in vivo animal studies have shown that there are toxic sideeffects in the tissues of the eye when anti-metabolites are used insufficiently high concentration to inhibit lens epithelial cellsproliferation. In attempts to avoid side effects on other ocular tissuesan immunotoxin specifically inhibiting proliferation of lens epithelialcells has been evaluated. The anti-lens epithelial cell monoclonalantibody binds specifically to lens epithelial cells and carries ricinor saporin that kill proliferating cells. In the experimental studies,antibodies against human antitransferrin and FGF have been used asantibodies against lens epithelial cells. However, no conclusive resultshave been obtained.

Another pharmacological approach is to separate lens epithelial cellsfrom the lens capsule. Ethylenediamine tetraacetic acid (EDTA) wasincluded in an irrigation solution and a simulated extracapsularcataract extraction was performed to separate lens epithelial cells. Inother attempts, EDTA was used with a viscoelastic material (U.S. Pat.No. 5,204,331 to Nishi et al., 1993), or simply introduced into the lenscapsule. When an EDTA solution was included in an irrigation solutionand a simulated extracapsular cataract extraction was performed incadaver eyes, the anterior lens epithelial cells could be separated.EDTA seems not to be more efficient than other agents evaluated in PCOprophylaxis.

Enzymes such as trypsin and DISPOSE (protease) have also been evaluatedfor separation of lens epithelial cells. When a 2% trypsin solution wasincluded in an irrigation solution and a simulated extracapsularcataract extraction was performed in cadaver eyes, lens epithelial cellswere stripped in places. The cell separation was partially successful.However, the zonules were damaged by the trypsin solution. The use of anactive enzyme can be a problem even when an enzyme solution isintroduced into the lens capsule because it can damage the zonules boundto the lens capsule.

According to U.S. Pat. No. 4,909,784 to Dubroff 1990, when acell-killing substance is introduced into the lens capsule through asmall hole, without first removing the lens, lens epithelial cells arekilled. A drawback when using this method is that the efficacy of thetreatment may be strongly limited, if the natural lens is not removedbefore administrating the cell-killing substance. The natural lens mayabsorb or decrease the efficacy of the substance due to the huge numberof lens epithelial cells within the lens. A viscoelastic material thatis introduced into the anterior chamber prevents the active agent fromescaping from the lens capsule, and prevents damage to the cornealendothelium. In related patents (U.S. Pat. No. 4,909,784 to Dubroff1990, U.S. Pat. No. 5,013,295 to Dubroff 1991), a syringe to remove theintroduced substance from the lens capsule through a small hole wasdisclosed. However, physically and technically, it seems to be difficultto efficiently remove the substance introduced into the lens capsulebefore capsulorhexis without damaging the lens capsule. The remainingsubstance may escape from the lens capsule and damage the cells andtissues facing the anterior chamber during and after capsulorhexis.

An important problem in connection with all methods relating to cataractsurgery is the difficulty of observing the interior of the lens capsule,especially behind the iris, in order to ascertain that measure takenwere successful, such as the removal of residual lens epithelial cells.

U.S. Pat. No. 5,651,783 (Reynard 1995) discloses a fiber optic sleevethat permits endoscope visualization of intraocular structures eitherthrough the surgical handpiece or through an end piece attachment.However, this patent is silent in regard of evaluating the capsularinside in a turbulent flow of irrigation solution and lens materialsflowing around the end of the fiber optic during the process ofphacoemulsification and irrigation-aspiration, and such evaluationappears very difficult given the premises in the patent.

Gwon et al, in J. Refract. Surgery, Vol. 19, November 1993, pp 735-746discloses that the lens capsule was expanded with air andperfluoropropane by closing a capsulotomy of a size 2.5 to 3.5 mm with apatch, attached to the capsule by Healon and overlapping the capsule byat least 1 mm. The reason was to study the effect on lens regenerationin rabbits and cats. Nothing was explained of using the technique inother aspects. Additionally, it seems difficult to use the technique ofclosing off the capsule with a patch for performing different procedureswithin the capsule, as the patch would block introduction of devicesinto the capsule and performance of different methods within thecapsule. Furthermore, the authors describe the situation that thecapsule is not completely filled by air, but a mixture of air andviscoelastic solution (Healon®).

In Green G F et al. Prevention of posterior capsular opacification byendocapsular circulation of chemical agents (WO 02/15828), priority 21Aug. 15, 2000, there is disclosed a tip is described for sealing a lenscapsule by forming a seal with the edge of a small capsulorhexis.

In Maaloof, A et al. A device for sealing the capsular bag of an eye anda method for delivering fluid or treatment substances to the lens of aneye (WO 02/43632 A1), priority 28 Nov. 2000, 19 Apr. 2001, there isdisclosed a plug is described for sealing the lens capsule and a methodfor flushing solutions or chemicals inside the lens capsule.

These patents are silent in regard of using a gas to expand the capsule,and also about delivering low doses of agent solutions to the lensepithelial cells situated at the capsular surface by the phenomenon ofsurface tension. It seems hazardous to flush or fill the capsulecompletely with an agent solution, because it exposes the patients' eyeto a high dose of the agent solution. There is also a risk that the plugor the tip get loose so that the agent solution leaks out into theanterior chamber and injures delicate tissues, such as the cornealendothelium. A drawback with using the described plug or tip is that nodevices can be introduced into the capsule after the plug or the tip hasbeen mounted at the capsule.

U.S. Pat. No. 5,061,696 to York discloses a method for destroying lensepithelial cells comprising using a double cannula for simultaneouslyaspirating aqueous and/or irrigating solution from the lens capsule,posterior chamber and anterior chamber, injecting an ocularlybiocompatible gas to fill the anterior chamber, posterior chamber andlens capsule with said gas, and then injecting via a separate cannula, ahypotonic viscoelastic substance to fill the lens capsule andosmotically destroy the lens epithelial cells without diluting thehypotonic viscoelastic with isotonic solutions in the eye

SUMMARY OF THE INVENTION

In one aspect of the invention there is provided a method for thesealing of the lens capsule of an eye combined with gas expansion of alens capsule. This was surprisingly found to have great advantages,before and during administration of an active agent solution into thecapsule. The method according to the invention is defined in claim 1. Byemploying a novel device according to another aspect of the inventiongas is prevented from leaking out from the capsule. The device accordingto the invention is defined in claim 1.

If gas leakage is observed, indicating that the device is not safelyattached at the capsulorhexis, it will be possible to avoidadministration of a toxic agent solution. For some devices the gasexpansion also strengthen the device-capsule contact by exerting a gaspressure to the device which in turn is pressed against the capsularsurface because of the lower pressure in the anterior chamber.

In one embodiment of the device according to the invention the device isa plug adapted to seal against the anterior surface of the lens capsule.

In another embodiment the device for sealing the capsule is a tip of aprobe with irrigation and aspiration capabilities.

In a third embodiment the device for sealing the capsule is a tube witha leakage preventing channel, and having the capability of permittingdifferent devices to be introduced into the capsule without leakage of agas or an agent solution from the capsule. Optionally, the tube cam becomposed of several lumens.

In a further aspect of the invention, there is contemplated the use oflow doses in the treatment of lens epithelial cells. Compared to priorart methods the dose can be reduced by a factor 5-10 and even 20 incertain circumstances. In a preferred embodiment a detergent is includedin the agent solution. Thereby, the administration of the solution tothe lens epithelial cells over/at the entire capsular surface isimproved, which allows a reduction of the dose by a factor 2 or more.

Further scope of applicability of the present invention will becomeapparent from the detailed description given hereinafter. However, itshould be understood that the detailed description and specificexamples, while indicating preferred embodiments of the invention, aregiven by way of illustration only, since various changes andmodifications within the spirit and scope of the invention will becomeapparent to those skilled in the art from this detailed description.

The present invention will become more fully understood from thedetailed description given hereinbelow and the accompanying drawingswhich are given by way of illustration only, and thus not limitative ofthe present invention, and wherein

FIG. 1 shows the device according to the invention in a side view;

FIG. 2 shows a coupling device for use in the invention; and

FIG. 3 shows a rotatable device usable with the device according to theinvention.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

The present invention relates to a method suitable for use in eyesurgery, and to a specific device and accessories connectable to thedevice and/or useable together with said device.

The method is based on a general principle, for which patent is appliedin PCT/SE02/00854, that is based on the use of e.g. gas to expand a lenscapsule and keep it expanded, for the purpose of performing varioussurgical procedures inside the capsule, e.g. administration of agentsfor the purpose of killing residual lens epithelial cells, that couldcause Posterior Capsular Opacification (PCO).

The novel method is an inventive combination of said general principleand the idea of sealing an eye with a sealing device or means, such asthe ones mentioned in the background section.

Thus, the invention relates to a method of eye surgery, which comprisesas a first step making an incision in the cornea or the sclera in orderto gain access to the interior of an eye. If it is desired to remove thelens, it will be necessary to make a capsulorhexis in the lens capsule.Thereafter, the lens is removed from the lens capsule of the eye, e.g.by phacoemulsification (ultra sound or laser), or by irrigation andaspiration or by extra capsular lens extraction (ECLE), or any othersuitable method.

When the lens has been successfully removed, it may be desirable toperform a number of different procedures inside the capsule, such as theabove mentioned killing and removal of residual cells, by administeringan active agent for killing any residual epithelial cells; working theinner surface of the lens capsule with a wiper device to physicallyrelease/detach any residual epithelial cells; or wiping the innersurface of the lens capsule with said device to dry out any unwantedresidual liquids, or spread an active agent solution over the innersurface.

In order to be able to perform these procedures in a simple andefficient way, it is convenient according to the invention to expand thecapsule with a gas. In order that this be possible, the capsule is firstsealed with an appropriate sealing means, to provide gas leakage proofsealing. The sealing can be achieved in different ways, all fallingwithin the scope of the invention. I.a. the devices disclosed in thepatent applications mentioned in the background are suitable.

However, there is also provided a novel leakage preventive device, bymeans of which it is equally possible to use a viscoelastic compound forsealing purposes.

EXAMPLES Example 1 Plug Sealing

General Experimental Procedure, Group A-D

In groups A to D, rabbits (2.0-2.5 kg mixed sex, New Zealand White) areused to illustrate the invention of PCO prophylaxis. Both eyes of therabbits are used, with a total of 10 eyes per test group. The eyes ofthe different groups are randomized between left and right eyes, andbetween first and second eye in the surgical performance.

Twenty minutes before administering the anaesthetic to a rabbit, thepupils are dilated by topical instillation of mydriatika (cyclopentolat7.5 mg/ml+phenylephrine 2.5 mg/ml). Anesthetic is given by i.m.injection of 2.0 ml ketamin solution (50 mg/ml) and 1.0 ml xylazinsolution (20 mg/ml). Iteration is given occasionally by a second i.m.injection of 0.50 ml ketamin solution. An operating microscope is usedto observe the surgery. Before surgery, tetrakain is instilled topically(5 mg/ml), as well as a second instillation of mydriatika. The cornealincision is made by a 3.0 mm angled slit knife. 0.1 ml of 1% heparinsolution (5000 IU) is injected into the anterior chamber to preventsynechiae. The anterior chamber is then expanded by injection of aviscoelastic solution (10 mg/ml hyaluronate; Healon). A continuouscurvilinear capsulorhexis (D=4 mm) is made using a pair of Corydonforceps, if not else is specified. Hydro dissection is made by injectionof balanced salt solution (BSS) between the capsule and the crystallinelens. The crystalline lens is removed by phacoemulsification followed bycapsular polishing using an anterior segment operating system (OertliQuinto, Oertli Instrumente AG, Berneck, Switzerland; Setting of a vacuumof 150 mmHg, a flow of 25 ml/min, a bottle height of 70 cm, and <70%phacoemulsification power at the ultrasound frequency of 28 kHz.).Balanced salt solution with 1.0 ml heparin solution (5000 IU) added, isused as irrigation solution during the lens tissue removal.

The anterior chamber is refilled with a viscoelastic solution based on10 mg/ml hyaluronate (Healon), except of specified groups where aviscoelastic solution of 23 mg/ml hyaluronate (Healon5) is used instead.

The agent solution is prepared the minutes before use, formed by a watersolution of saponin from Quillaja bark (1 mg/ml) and trypan blue (1mg/ml). Trypan blue is used to make it possible to identify the agentsolution through the operating microscope. Saponin has two importantcharacteristics, that has detergent and cell lysis capabilities.

After the performed treatment according to Groups A to D presentedbelow, the rabbits are killed by i.v. injection of 5 ml pentobarbitalsolution (100 mg/ml). The eyes are enucleated, fixated in 2.5%glutaraldehyde, and embedded in historesin for histological evaluation.

Group A: Plug Sealing and Gas Expansion

A plug according to WO 02/43632 A1 (Maloof) connected to a tube withseveral lumens is attached at the capsulorhexis to seal the capsule, andused in Groups A-D. The capsule is expanded by injection of 0.2 ml gas(air). The gas is introduced through the plug into the capsule via thetube. If no gas leaks out of the capsule, the capsular sealing by theplug is more reliable. Gas leakage indicates that the plug is notproperly mounted or that the plug is defect. Prevented gas leakageguarantees a sealed capsule before introducing an active agent solution.

0.03 ml of the active agent solution is applied to the inner surface ofthe capsule through the tube and the plug. The solution is administratedefficiently along the inner capsular surface by the phenomenon ofsurface tension. After one minute of exposure, the agent solution isremoved by continuous irrigation and aspiration with BSS inside thecapsule using an Oertli Quinto operating machine connected to the tubeand the plug.

In the histological evaluation, it is observed that the lens epithelialcells are severely damaged by ruptured cell membranes by the effect ofsaponin, including the cells attached to the anterior surface of thecapsule. No damage is observed on any other tissue outside the capsule,such as corneal endothelium, iris, ciliary process or retina.

The small dose and volume of the agent solution is most likely to beenough to cover the entire capsular surface. The observed gas leakageindicates that the administration of the agent solution should bestopped and thereby leakage of the agent solution is prevented.

Group B: Plug Seating without Gas Expansion

A plug connected to a tube with several lumens is attached at thecapsulorhexis to seal the capsule. 0.03 ml of the active agent solutionis injected into the capsule through the tube and the plug. A smallvolume of the agent solution accidentally leaks out to the anteriorchamber between the plug and the capsule and the toxic agent solutionreaches the iris in the anterior chamber. In the rest of the eyes, theadministration of the agent solution is successful only in the centralregion of the capsule. It does not reach peripheral regions of thecapsule. Neither is any spreading by surface tension along the innercapsular surface observed. After one minute of exposure, the agentsolution is removed by continuous irrigation and aspiration of BSSinside the capsule using the Oertli Quinto operating machine connectedto the tube and the plug.

In the histological evaluation, it is observed that the lens epithelialcells are damaged by ruptured cell membranes, but not for cells situatedat peripheral regions of the capsule. No damage is observed on othertissues outside the capsule, such as corneal endothelium, iris, ciliaryprocess or the retina, except for tissues, including the cornealendothelium, in the eyes in which leakage has been observed.

The used dose and volume of the agent solution are not enough forefficient distribution to the lens epithelial cells inside the capsuleby this technique. There seems also to be a risk of accidental leakageof an agent solution from the capsule, with no previous signals of aleaking capsule, compared to the use of gas expansion of the capsulebefore the delivery of the agent solution as in Group A.

Group C: Plug Sealing and Expansion by Agent Solution

A plug connected to a tube with several lumens is attached at thecapsulorhexis to seal the capsule. 0.2 ml of the active agent solutionis injected into the capsule through the tube and the plug, therebyexpanding and completely filling the capsule by the agent solution. Nospreading of the agent solution by surface tension along the capsularsurface is observed. A leakage of agent solution between the plug andthe capsule is observed, as a consequence of a failed mounting of theplug to the capsule. The agent solution reaches several delicate tissuesin the anterior chamber, including parts of the corneal endothelium.

The agent solution is removed from the capsule after one minute ofexposure by continuous irrigation and aspiration of BSS inside thecapsule using the Oertli Quinto operating machine connected to the tubesand the plug.

In the histological evaluation, it is observed that the lens epithelialcells are damaged by ruptured cell membranes, also at the anteriorcapsular surface and at peripheral regions of the capsule. No damage isobserved on other tissues outside the capsule, such as cornealendothelium, iris, ciliary process or the retina, except for the eyes inwhich leakage has been observed, in which tissues, including the cornealendothelium, has been injured. The dose and volume of the agent solutionused is enough for efficient distribution to the lens epithelial cellsinside the capsule by this technique. However, it seems to be a risk ofaccidental leakage of the agent solution from the capsule, and with noprevious signals of the leaking capsule, which is given by gas expansiondemonstrated in group A.

Group D: Plug and Viscoelastic Seating and Gas Expansion

Instead of a viscoelastic solution of low concentration hyaluronate (10mg/ml; Healon), as being used in Group A, a viscoelastic solution ofhigh concentration hyaluronate (23 mg/ml; Healon5) is introduced intothe anterior chamber after lens removal.

A plug connected to a tube with several lumens is attached at thecapsulorhexis to seal the capsule. The capsule is expanded by injectionof 0.2 nil gas (air). The gas is introduced through the plug into thecapsule via the tube. Gas is prevented to leak out of the capsule, asthe sealed capsule is highly reliable, by using both a plug and aviscoelastic solution, indicating that an active agent solution can beintroduced without any harm.

0.03 ml of the active agent solution is applied to the inner surface ofthe capsule through the tube and the plug. The solution is administratedefficiently along the inner capsular surface by the phenomenon ofsurface tension, enhanced by the detergent saponin. After one minute ofexposure, the agent solution is removed by continuous irrigation andaspiration with BSS inside the capsule using an Oertli Quinto operatingmachine connected to the tube and the plug.

In the histological evaluation, it is observed that the lens epithelialcells are severely damaged by ruptured cell membranes by the effect ofsaponin, including the cells attached to the anterior surface of thecapsule. No damage is observed on any other tissue outside the capsule,such as corneal endothelium, iris, ciliary process or retina. Results ofGroup A to D Agent Observed Plug Gas Agent Gas solution spread ofObserved Treatment Group sealing expansion solution leakage leakagesolution injuries of LEC A Yes Yes 0.03 ml Sometimes None entire NoneGood capsular surface B Yes No 0.03 ml — Sometimes central SometimesPoor capsular but small region C Yes No 0.2 ml — Sometimes filledSometimes Good capsule and severe D* Yes Yes 0.03 ml None None entireNone Good capsular surfaceD* = The anterior chambers are filled with viscoelastic solution of 23mg/ml hyaluronate (Healon5, Pharmacia, Uppsala, Sweden).

The conclusion is, in respect of safety and treatment efficacy, topreferably use the method of group D. That is to use plug sealing and aviscoelastic solution with high concentration of hyaluronate (23 mg/ml)within the anterior chamber, combined with a gas expanded capsule and alow dose and volume of the agent solution.

Example 2 Tip Sealing

This experiment is similarly performed according to the descriptionpresented in Example 1. This means that groups E to H in this experimentcorrespond to the groups A to D in Example 1, except for making asmaller capsulorhexis (D=1.5 mm), using a lens removal system for smallincision surgery, a device with an impeller (Ref. Baush & Lombsinstrument, with the Catarex System) instead of using the Oertli Quintooperating machine, and using a tip instead of a plug to seal thecapsule. The instrument was equipped with additional lumens for gas andagent solution delivery. Results of group E to H Agent Observed Tip GasAgent Gas solution spread of Observed Treatment Group sealing expansionsolution Leakage leakage solution injuries of LEC E Yes Yes 0.03 mlSometimes None entire None Good capsular surface F Yes No 0.03 ml —Sometimes central Sometimes Poor capsular but small region G Yes No 0.2ml — Sometimes filled Sometimes Good capsule and severe H* Yes Yes 0.03ml None None entire None Good capsular surfaceH* = The anterior chambers are filled with viscoelastic solution of 23mg/ml hyaluronate (Healon5, Pharmacia, Uppsala, Sweden).

The conclusion is, in respect of safety and treatment efficacy, topreferably use the method used in group H. That is to use tip sealingand a viscoelastic solution with high concentration of hyaluronate (23mg/ml) within the anterior chamber, combined with a gas expanded capsuleand a low dose and volume of the agent solution.

Example 3 Tube Sealing

This experiment is similarly performed according to the descriptionpresented in Example 1. This means that groups I to L in this experimentcorrespond to the groups A to D in Example 1, except for making asmaller capsulorhexis (D=1.5 mm), using a lens removal system for smallincision surgery, a device with an impeller (Ref. Baush & Lombsinstrument) instead of using the Oertli Quinto operating machine, andusing a tube with a leakage preventive canal, instead of a plug to sealthe capsule. In this example no additional lumens were included in theimpeller device. Results of group I to L Agent Observed Tube Gas AgentGas solution spread of Observed Treatment Group sealing expansionsolution Leakage leakage solution injuries of LEC I Yes Yes 0.03 mlSometimes None entire None Good capsular surface J Yes No 0.03 ml —Sometimes central Sometimes Poor capsular but small region K Yes No 0.2ml — Sometimes filled Sometimes Good capsule and severe L* Yes Yes 0.03ml None None entire None Good capsular surfaceL* = The anterior chambers are filled with viscoelastic solution of 23mg/ml hyaluronate (Healon5, Pharmacia, Uppsala, Sweden).

The conclusion is, in respect of safety and treatment efficacy, topreferably use the method used in group L. That is to use tube sealingand a viscoelastic solution with high concentration of hyaluronate (23mg/ml) within the anterior chamber, combined with a gas expanded capsuleand a low dose and volume of the agent solution.

Example 4 Viscoelastic Solution Sealing

This experiment is performed in accordance with the description of theGeneral Experimental Procedure presented in Example 1, but with newmethods for the groups M to Q specified below.

Group M: Viscoelastic Solution Sealing without Gas Expansion

0.03 ml of the active agent solution is injected into the capsule. Thesolution does not spread to peripheral regions of the capsule. Neitheris any spreading of the solution by surface tension along the innercapsular surface observed. Minor leakage of agent solution into theanterior chamber is also observed, whereas the solution reaches delicatetissues such as the iris. After one minute of exposure the agentsolution is removed by continuous irrigation and aspiration of BSSinside the capsule using the Oertli Quinto operating machine and an I/Atip.

In the histological evaluation, it is observed that lens epithelialcells close to the capsulorhexis are damaged by ruptured cell membranes,but the treatment is incomplete. Damages are observed on other tissuesof the anterior chamber, such as the iris.

The distribution of the agent solution is not efficient by thistechnique to treat all lens epithelial cells inside the capsule. Leakageof an agent solution from the capsule to the anterior chamber is evidentby this technique.

Group N: Viscoelastic Solution Sealing without Gas Expansion

0.2 ml of the active agent solution is injected into the capsule.However, the solution does not spread to peripheral regions of thecapsule. Neither is any spreading of the solution by surface tensionalong the inner capsular surface observed. Severe leakage of agentsolution into the anterior chamber is also observed, whereas thesolution reaches delicate tissues such as the corneal endothelium. Afterone minute of exposure the agent solution is removed by continuousirrigation and aspiration of BSS inside the capsule using the OertliQuinto operating machine and an I/A tip.

In the histological evaluation, it is observed that lens epithelialcells close to the capsulorhexis are damaged by ruptured cell membranes,but the treatment is incomplete. Damages are observed on other tissuesof the anterior chamber, such as corneal endothelium and the iris.

The distribution of the agent solution is not efficient by thistechnique to treat all lens epithelial cells inside the capsule. Leakageof an agent solution from the capsule to the anterior chamber is evidentby this technique.

Group 0: Deficient Viscoelastic Solution Sealing and Gas Expansion

0.2 ml gas (air) is injected into the capsule. It is observed that thegas leaks out of the capsule into the anterior chamber, indicating an-on-successful sealing of the capsule. The conclusion is that aviscoelastic solution of 10 mg/ml hyaluronate (Healon) is not enough toprevent gas leakage. 0.03 ml of the active agent solution was injectedinto the capsule. The leakage of agent solution into the anteriorchamber is observed, and is enhanced by remaining gas bubbles inside theanterior chamber. The agent solution is removed after one minute ofexposure by continuous irrigation and aspiration of BSS inside thecapsule using the Oertli Quinto operating machine and an I/A tip.

In the histological evaluation, it is observed that the lens epithelialcells close to the capsulorhexis are damaged by ruptured cell membranes,but the treatment is incomplete in peripheral regions of the capsule.Some damages are observed on other tissues of the anterior chamber, suchas corneal endothelium and the iris.

The distribution of the agent solution is not efficient to treat alllens epithelial cells inside the capsule, and leakage of the agentsolution from the capsule to the anterior chamber is evident using thistechnique.

Group P: Viscoelastic Solution Sealing (23 mg/ml) and Gas Expansion

0.2 ml gas (air) is injected into the capsule. It is observed that thegas does not leak out of the capsule into the anterior chamber,indicating a successful sealing of the capsule by the viscoelasticsolution of 23 mg/ml hyaluronate. 0.03 ml of the active agent solutionis injected into the capsule. The observation through the operatingmicroscope is similar to Group A, Example 1. The agent solution isremoved after one minute of exposure by continuous irrigation andaspiration of BSS inside the capsule using the Oertli Quinto and an I/Atip. In the histological evaluation, it is observed that the lensepithelial cells are severely damaged by ruptured cell membranes,including the cells attached to the anterior surface of the capsule,similar to the results of Group A, Example 1. No damages is observed onany other tissue outside the capsule, such as corneal endothelium, iris,ciliary process or the retina.

The small dose and volume of the agent solution is most likely to beenough to cover the entire capsular surface.

Group Q: Viscoelastic Solution Sealing (25 mg/ml) and Gas Expansion

This experimental group is performed as group L, but a viscoelasticsolution of higher concentration of hyaluronate (25 mg/ml; MicroviscPhaco) is used instead to fill the anterior chamber. The observationindicates a slight improvement of preventing leakage of agent solutionwhen using a viscoelastic solution of 25 mg/ml hyaluronate than of 23mg/ml. Results of group M to Q Viscoel. Agent Observed solution GasAgent Gas solution spread of Observed Treatment Group sealing expansionsolution leakage leakage solution injuries of LEC M Yes No 0.03 ml —None central Yes, but Poor 23 mg/ml capsular small region N Yes No 0.2ml — None central Yes Medium 23 mg/ml capsular region O* Yes Yes, but0.03 ml Yes, Yes central Yes, but Poor 10 mg/ml failed severe capsularsmall region P Yes Yes 0.03 ml No Sometimes entire Sometimes Good 23mg/ml capsular but small surface Q** Yes Yes 0.03 ml No Few entireFew_and Good 25 mg/ml capsular small surfaceO* = The anterior chambers are filled with viscoelastic solution of 10mg/ml hyaluronate (Healon).Q** = The anterior chambers are filled with viscoelastic solution of 25mg/ml hyaluronate (Microvisc Phaco).

The conclusion is, in respect of safety and treatment efficacy, topreferably use the method used in group Q. That is to use tip sealingand a viscoelastic solution with high concentration of hyaluronate (25mg/ml) within the anterior chamber, combined with a gas expanded capsuleand a low dose and volume of the agent solution.

Example 5 Worse Cases of Agent Solution Administration

This experiment is performed in accordance with the description of theGeneral Experimental Procedure presented in Example 1, but with thegroups R and S specified below.

Group R: Low Dose Failure

0.03 ml of the agent solution is placed at the capsulorhexis to simulateworse case of a low dose agent solution injection. It is observed thatthe agent solution is spread locally around the spot of injection,reaching to the iris. Directly, irrigation and aspiration is performedby a I/A tip inside the anterior chamber. After 4 seconds, at a flow of25 ml/min, the 0.03 ml agent solution is quickly diluted with a factorof 50 or higher, and removed by aspiration at an equivalent proportion.The outcome is evaluated by histological examination, in which it isobserved some injuries to the iris and to the corneal endothelium closeto the corneal incision.

Group S: High Dose Failure

0.2 ml of the agent solution is placed at the capsulorhexis to simulateworse case of a high dose agent solution injection. It is observed thatthe agent solution is spread in a far more extent than in the eyes inGroup N, reaching the corneal endothelium and the iris. After 4 seconds,at a flow of 25 ml/min, the 0.2 ml agent solution is diluted with afactor of 8 or higher, and removed by aspiration at an equivalentproportion. The outcome is evaluated by histological examination, inwhich it is observed severe injuries to the iris and to the cornealendothelium, most extensively at the corneal incision. Results of GroupR and S Viscoel. Observed Histologic solution in Gas Agent spread ofDilution indication Group AC expansion solution solution I/A in ACfactor* of injuries R Yes No 0.03 ml local 4 sec 50 Yes, some region inAC S Yes No 0.2 ml more 4 sec 8 Yes, extensively severe in AC*= The effect of aspiration has not been considered, which would levelup the dilution factor even further.

For safety reason, the dose of GroupR, low dose and volume, shouldpreferably be used.

Now the devices forming part of the inventive concept and usable withthe method according to the invention will be described in detail withreference to the drawings.

Now the leakage preventive device according to the invention will bedescribed in closer detail with reference to FIGS. 1-3.

A leakage preventive device has been found to facilitate and increasethe safety to perform manipulations within a lens capsule and toadminister gases and solutions into the lens capsule, especially whenthe surgery includes a lens capsule expanded by a gas.

The leakage preventive device allows the introduction of gases,solutions and different devices (surgical instruments, tools, wipers,patches, absorbing pieces, intraocular implants, intraocular lensmolding materials and so forth), and prevent leakage of gases andsolutions out of the lens capsule, preferably simultaneously. This isespecially important when the lens capsule is expanded by a gas.

Overall Description

The leakage preventive device 10, shown in FIG. 1, having a proximal endP and a distal end D, includes a tube 12 with a proximal portion and adistal portion and a central axis C. Furthermore, for purpose of ease ofunderstanding, the device will be described as having an upper half anda lower half, whereby the dividing plane is through the device in itslongitudinal extension, and upper and lower is with respect to theorientation of the device as shown in FIG. 1. The tube is hollow withone or several lumens 14 extending between the proximal end and thedistal end. At least one lumen is a leakage preventive lumen. Theleakage prevention is achieved by one or several barriers 16 within thelumen 14, the details of which will be elucidated in detail below. Theproximal end includes a funnel 18 which enables and facilitatesimplantation of the leakage preventive device, and also the connectingof different secondary devices and/or the introduction of other devicesinto the leakage preventive lumen.

In a preferred embodiment the distal end includes a lid membrane 20which is adapted to close the capsulorhexis opening of the lens capsule.The lid membrane 20 is preferably separable from the tube 12 of theleakage preventive device, thereby providing a closure for thecapsulorhexis opening even after the leakage preventive device has beenremoved from the eye. This is important when an intraocular lens implantis molded within the lens capsule by an injected lens forming fluid. Byproviding a circumferential groove or depression in the tube 12 nearsaid lid membrane, it will be an easy matter to cut off the membranewhen the operation is finished. The lid 20 can have a cut out or slitenabling passing of devices and gas through said lid.

The leakage preventive device is preferably made of one or severaldifferent materials such as polyurethane, silicone,hydroxymethylmethacrylate, polymide, polymethylmethacrylate,polyethylene, polyester, polystyrene, polypropylene,polytetrafluorethylene, ethylene-vinyl-acetate or equivalent.Furthermore the material may have adhesive qualities, and preferably itshould be pliable, resilient and non-absorbent, i.e. it should notabsorb any of the liquids or agents that it may come into contact withduring use.

In use, the device is inserted through an incision of the eye, such as acorneal or a scleral incision. When properly located, the proximal endand the funnel are located outside the incision, and the distal portionof the tube is located within the eye. Thereby, the proximal portion ofthe tube extends through the incision into the anterior chamber, and thedistal portion extends within the anterior chamber towards the lenscapsule and the distal end is directed to or into a lens capsularopening.

Tube

The leakage preventive device includes a tube 12 having a proximalportion and a distal portion extended between the proximal end and thedistal end of the leakage preventive device. The tube may have across-sectional dimension of about 0.5 to 3 mm such as about 1.5 mm. Thetotal length of the tube is preferably in the range of 5 mm to 15 mm,such as about 7 mm.

The tube is preferably made of a non-absorbent material such aspolyurethane, silicone or equivalent. Furthermore the material may haveadhesive properties, and should preferably be pliable and resilient.However, the tube should be stiff enough to avoid undesired wrinklingwhen being used.

The tube is hollow and includes one or several lumens 14 extending fromthe proximal end to the distal end. The purpose of the lumens is toallow devices (surgical instruments, intraocular implants and so forth)to be moved through the tube, as well as solutions and gases.

At least one lumen should prevent the leakage of liquids and/or gasesoutwards through the tube. The purpose is to allow moving differentinstruments (surgical instruments, cannulas, threads, wipes, dryingsticks, tips and so forth) through the tube and preferably at the sametime to prevent gases or solutions to leak out, preferably in asimultaneous fashion.

Lumen Barriers

The leakage preventive capability of the lumen is obtained by one orseveral barriers 16. The barriers can be of different kinds, such asviscoelastic solutions 17 occupying the lumen, in which case the highviscosity makes it possible to provide the barrier. Other possibilitiesare membranes 20 covering the opening of a lumen, flattened passages 22within a lumen, narrow passages in a lumen, valves, flap valves just tomention a few possiblities. Barriers such as membranes, flattenedpassages, narrow passages, valves, flap valves can be positioned at oneor both ends of the lumen or somewhere between the proximal end and thedistal end. When the barriers are provided as e.g. viscoelasticsolutions, flattened passages, narrow passages they can extend along thewhole lumen or partial regions of the lumen. It would pertain to thefield of the man skilled in the art to provide other kinds of barrierswith equivalent function to be used for the same purpose.

Several barriers can be included simultaneously to improve the leakagepreventive capability. For example, a viscoelastic solution along thelumen enclosed by a flattened passage at the proximal portion and a flapvalve at the distal end, would very efficiently prevent leakage of gasesand solutions. Furthermore, the distal and proximal barriers also serveto retain the viscoelastic solution in the lumen when differentinstruments are moved through the viscoelastic solution.

One important criterion of all barriers is that it should be possible toforce secondary devices through the barriers, and that the barrier stillwould prevent leakage of solutions and gases, preferably simultaneously.

To improve the passing of devices through the barriers, it is preferredthat the friction between the inner surface of the lumen and passingdevices is low, or at least as low as possible. A viscoelastic solutioninside the leakage preventive lumen has the additional advantage ofserving as a lubricant.

Funnel

At the proximal end there is a funnel 16 which includes a wide opening,narrowing gradually into the leakage preventive lumen of the tube 12.The funnel 16 has a shape that facilitates the insertion of differentinstruments into the lumen. Suitably, the shape is a symmetric conicalshape 15.

The outer diameter of the wide opening is preferably in the range of 3to 15 mm, such as 7 mm. It is then gradually decreased to the dimensionof the proximal part of the tube. The length of the funnel is preferablyin the range of 0.5 to 15 mm, such as 4 mm.

The funnel may have a shape that is suitable for connecting differentinstruments to the leakage preventive device, such as anirrigation/aspiration device. The funnel may have different connectingoptions, such as Luer Lock® 24, threads, slots or equivalent.

The funnel 18 can form an angle with respect to the tube in the range 0to 45°. Preferably the angle is selected such that when the device isproperly positioned in the eye, the funnel is perpendicular to thesurface of the eye globe at the point of insertion. For ease ofhandling, e.g. guiding, rotation and holding the device, the angle is0°. The device will also be easier to manufacture in the latter case.The skilled man will at any rate be able to design the device with afunnel angle that is suitable for a desired purpose.

In one preferred embodiment, the funnel is provided with a grippingmeans 26, suitably in the form of a short pin or protrusion, located atthe periphery of the funnel 18, near or at the opening, and having alength in the range of 2 to 30 mm, preferably 8 mm. The purpose of thegripping means 26 is to allow guiding, holding and/or rotating theleakage preventive device, such as by a pair of forceps. The grippingmeans can also have a shape that allows fixation of the tube to the eye,such as a connector member (not shown) that can be connected to an eyelid holder or equivalent.

In another preferred embodiment of the device, there are fixation means29 for temporary fixation of the leakage preventive device to the eyeglobe, such as loops attached to the funnel, thin flaps extendinglaterally from the funnel, optionally having holes for sutures, to whicha suture easily can be attached for fixation by some stitches to thescleral region of the eye globe. Adhesive elements is also envisaged forattaching to the scleral region.

In another preferred embodiment, the funnel comprises a coupling means,to enable quick and controlled attachment and release of secondarydevices to/from the funnel, or other devices introduced into the leakagepreventive lumen. The coupling means can comprise magnets, spring drivencatchers or equivalent.

In one preferred embodiment, shown in FIG. 2, the coupling meanscomprises one or several integrated permanent magnets 42 positioned atthe wide opening of the funnel, such as a magnetic ring at the edgearound the opening. By using the interaction between the differentpolarities of the magnets (+/−), a secondary device 46 with one orseveral (electro)magnets 44 can be forced to join the leakage preventivedevice, by magnetic attraction, or separated from it by a controlledoperation, such as by changing the polarity of the electromagnet 44 ofthe secondary device 46, causing magnetic repelling. For example, thejoin and release function is valuable for application in implantersdesigned to, temporary implant a leakage preventive device into an eye.

In still another preferred embodiment, the funnel has a drip edge at thewide opening that prevents any drops of agent solutions to flow from thefunnel to the surrounding tissues. For example, a colored agent solutionmay be easily identified and removed from the funnel.

Catcher

In one preferred embodiment a fixation member 28 (FIG. 1) is provided atthe proximal portion of the tube 12. The purpose of the fixation memberis to keep the device in a correct position at the incision of the eyeduring surgery.

The fixation member may be designed as a wedge shaped rim element thatis positioned at the lower half of the proximal portion of the tube 12,in a position that will be within the eye, grabbing with its hook end atthe posterior surface of the cornea or equivalent region of the eyeglobe. The wedge is preferably made of the same material as the tube,not excluding the possibility that other materials are possible.

The catcher can be provided by a flattened or narrowed passage 22 of thetube with the capability of serving as a lumen barrier.

It is highly desirable to increase the fixation during any movement(e.g. rotation) of devices within the leakage preventive device. Inorder to enhance the fixation, the proximal portion of the tube in onepreferred embodiment is provided with a fixation portion that includesfrosted and/or textured surfaces of the tube, to increase the frictionbetween the device and surrounding tissue. Preferably, portions of thesurface or the entire surface of the flattened or narrowed portions ofthe tube are frosted and/or textured. The frosted surface portions canbe continuous or non-continuous with other portions. Various designs ofthe frosted surface portions exist, for example, they can includestripes, checkerboard, dots, circles, triangles, squares, pentagons,octagons, lattice or virtually any other type of design. The frostingcan be provided on the front, back and/or edge surfaces. The frostedand/or textured surface portions can be applied to the proximal tubeportion by various methods including molding or surface texturing.Specifically, surfaces of the mold can be frosted or textured (e.g.sandblasting, electrode discharge machining (EDM), shot peening, laseretching chemical etching, sputtering, vapor depositing, etc.).Alternatively or in addition, the surfaces of the proximal tube portioncan be frosted or textured by; for example, sandblasting, shot peening,chemically etching, chemically etching portions to become frosted ornon-frosted, surface modifying or other various techniques to makeportions of the haptic lightly frosted or textured, medium frosted ortextured, highly frosted or textured, or frosted or textured to anydegree there between. The frosted and/or textured surface portions ofthe proximal tube portion increase friction in the interface between theproximal tube portion of the leakage preventive device and the cornealincision, to improve the fixation of the leakage preventive device atthe corneal incision or equivalent incision of the eye globe.

Lid Membrane

The lid membrane 20, is provided at the distal end of the tube 12,covering the opening thereof, and has an extension such that it coversand overlaps the capsulorhexis. It is preferably provided with means forproviding a self closing opening, such as a slit, flap valves, narrowingor so forth. In order to be easily separated from the tube of theleakage preventive device, when the medical procedure is terminated,there is preferably provided a circumferential groove 27 or recessaround the tube 12 near the lid 20. The material for the lid ispreferably having a light refraction index similar to the material ofinjectable intraocular lenses, in order that it will not cause anydisturbance. Preferably it has an oval shape which makes it easilyinsertable through a lumen in the tube 12 of the device 10.

Rotatable Device

In order to render the method according to the invention as efficient aspossible, e.g. to ascertain that lens epithelial cells be killed at thehighest possible rate, or to wipe the inner surface dry, or toadminister an agent solution at the interior surface of the lenscapsule, physically remove any residual cells that might adhere insidethe lens capsule, it would be attractive to be able to access theinterior via the leakage preventive device. This can be achieved byproviding the leakage preventive device with a rotatable device 30,illustrated in FIG. 3 a).

This rotatable device 30 is insertable into the lens capsule via one ofthe lumens in the tube. Thus, the purpose is to use the device forsurgical manipulations within the lens capsule, preferably expanded by agas, and preferably to prevent leakage of gases and solutions from thelens capsule during such operations. Examples of surgical manipulationsto be executed by the device inside the lens capsule are wiping, dryingor administrating an agent solution at the interior surface of the lenscapsule. The rotatable device is movable within the lumen (such asrotation in both directions and movements along the lumen, into and outof it and through it) and able to be separated from the tube.

Overall Description

The rotatable device 30 includes A) a shaft 31 having a proximal end anda distal end, B) a grip 32 in the proximal end to facilitate movementand rotating forces to the rotatable device and/or solutions and gases,and C) a connector member 33 in the distal end for attachment ofaccessories. The total length of the rotatable device 30 is longer thanthe length of the lumen 12, such as 8 mm and above.

In one preferred embodiment the rotatable device includes an extensionat the distal end, instead of a connector, comprising a desiredaccessory, such as a wiper.

Shaft

The rotatable device includes a shaft 31 having a proximal end and adistal end and a central axis extending between the ends. The shaft ishomogenous and is preferably formed as a thread or a stick, though itmay also be hollow. It is made of a material with torsion resistantproperties to allow a transferred rotating force of movement along theshaft. Examples of suitable materials are metal, nylon, polystyrene,polymethylmethacrylate (PMMA) or equivalent material with similarproperties. The diameter of the shaft is smaller than the inner diameterof the leakage preventive lumen, preferably a dimension of 0.1 to 1.5mm, such as 0.3 mm.

In one preferred embodiment, the shaft is flexible, referring to theability of bending the shaft along the central axis, but still havingthe torsion resistant properties.

In another preferred embodiment the shaft is hollow including one orseveral capillary lumens 34 extending from the proximal end to thedistal end, preferably having a dimension of about 0.1 to 1 mm, such as0.2 mm. The purpose of the lumens is to transfer solutions and gasesinto and out of the lens capsule. In such cases, the lumens at theproximal end should preferably be connected to another device forinjecting solutions or gases, or for aspirating those. This device canalso be a part of the rotatable device.

Grip

At the proximal end of the shaft there is a grip 32 that facilitatesrotation and movements of the shaft 31, by hand or by mechanical force.The grip is preferably formed as a handle, a knob for manual operation.Alternatively, it can be designed such that it enables connecting asecondary device to facilitate or create movements and/or rotation. Thegrip is preferably made of the same material as the shaft, but othermaterials are also useable to achieve a grip with said properties. Ifthere is one or more lumens in the shaft, the grip is adapted to fitsecondary devices.

Connector Member

At the distal end of the shaft there is provided a connector 33. Theshaft 31 and the connector 33 can be made in one piece or they can bemade in two separate parts joined together by physical or chemicalbonding, such as by glue, friction, threads, splines or the equivalent.The connector enables attachment of accessories to the rotatable device,such as a wiper, a piece of absorbing material and so forth. Theconnector enables the transfer of movements and rotating forces from therotatable device to the attached accessory.

In one embodiment, the connector simply comprises a ring member attachedto the distal tip of the shaft.

The outer measures of the ring should be smaller than the innerdimension of the lumen, into which the rotatable device is aimed to bepositioned. Different accessories can easily be attached to the ring bysimply passing the accessory through the ring such that the ringencircles a body portion of said accessory. If made by a suitablematerial, such as soft silicone, the accessory can be provided withlocking rims cooperating with the ring to hold the accessory in placeduring operation, while still being easily removed again.

In the use of the leakage preventing device, the rotatable device and anaccessory, the rotatable device with the attached accessory is forcedthrough the lumen with the barriers of the leakage preventing device. Inthis procedure the accessory is folded backwards at the lumen entranceof the funnel and the resilient material of the accessory allows it tobe stretched and extended inside the lumen. Once it has passed thelumen, the accessory will retain the desired shape within the lenscapsule to execute a manipulation, such as delivering an agent solution,wiping the interior surface of the lens capsule and so forth.

Wiper

In one preferred embodiment, the accessory is a wiper 35, shown in FIG.3 b), with a central body 36 and one or several loops 37 extending fromthe central region 36. Preferably the central body 36 has a narrowedwaistline 38, in order to retain the central body 36 in its position inthe connector.

In another preferred embodiment, the rotatable device and a specificaccessory, such as a wiper, is made in one piece or pieces attached toeach other more permanently by physical or chemical binding, such as byglue, friction or equivalent.

In another preferred embodiment, the distal end of the shaft of therotatable device is formed as a wiper, such as a pre-shaped thread thatwill return into desired shape once introduced into the lens capsule.

In still another preferred embodiment, the wiper is a type of formableresilient device including a central portion and two loop-type hapticportions. The haptic and the central portions are preferably made ofresilient material, for example, polyurethane, polypropylene, polyimide,polymethylmethacrylate (PMMA), silicone elastomer, hydrogel polymer,collagen containing polymer material (e.g. Collamer), organic orsynthetic gel compounds, polyurethane elastomer or other suitablebiocompatible materials. The haptic and the central portions can be madeof the same material or different. The haptic portions are anchored inthe lens portion, if not molded in one piece. The anchoring process issuch that the haptic portions remain securely anchored in the centralportion during wiper movement (such as through a lumen), wiper rotation,and throughout the surgical-use of the wiper.

The haptics are preferably C-shaped, however, other suitable hapticdesigns can be substituted for the ones shown. For example, the centralportion can be provided with several connecting portions located at endsof the central portion, and the haptics can be full loops anchored atboth ends to a pair of the connecting portions. Alternatively, thehaptic can be a ring connected to the central portion, such as bybridging haptic portions

The haptic portions can have the shape and profile shown in FIG. 3.However, other shapes and configurations of the haptic portions arepossible. Other suitable haptic portions are shown in U.S. Pat. Nos.4,573,998, 4,702,244, and 5,776,191 to Dr. Thomas R. Mazzocco,incorporated herein by reference.

One preferred embodiment according to the present invention utilizeshaptic portions made from polyimide sheet material in combination with acollagen containing polymer lens material (e.g. “Collamer”). The“Collamer” material is disclosed in detail in U.S. Pat. Nos. 5,654,349,5,654,363, 5,654,388, and 5,661,218 to Vladir Feingold and Alexi V.Osipov, incorporated herein by reference. The different parts canpreferably be made in one piece by the same material in all parts.

Haptic Portions

The haptics include a pair of stems extending radially from the centralportion on diametrically opposed sides, the stems being disposed in asubstantially horizontal plane.

In one preferred embodiment, the stems are generally round incross-section.

Frosted Haptic Surface Portions

In one preferred embodiment the wiper is provided with haptic portionsthat include frosted and/or textured surfaces. Specifically, portions ofthe surfaces or the entire surfaces of the haptic portions are frostedand/or textured. The frosted surface portions can be continuous ornon-continuous with other portions. Various designs of the frostedsurface portions, for example, can include stripes, checkerboard, dots,circles, triangles, squares, pentagons, octagons, lattice or virtuallyany other type of design including potentially art work. The frostingcan be provided on the front, back and/or edge surfaces.

The frosted and/or textured surface portions can be applied to thehaptic portions by various methods including molding or surfacetexturing. Specifically, surfaces of the mold can be frosted or textured(e.g. sandblasting, electrode discharge machining (EDM), shot peening,laser etching-chemical etching, sputtering, vapor depositing, etc.).Alternatively or in addition, the surfaces of the haptic portions can befrosted or textured by, for example, sandblasting, shot peening,chemically etching, chemically etching portions to become frosted ornon-frosted, surface modifying or other various techniques to makeportions of the haptic lightly frosted or textured, medium-frosted ortextured, highly frosted or textured, or frosted or textured to anydegree there between.

The frosted and/or textured surface portions of the haptic portionsincrease friction in the interface between the lens capsule and thehaptic portion to increase the extent of wiping capacity to affect lensfiber cells and/or the epithelial cells. It is highly desirable toincrease the wiping power during any relevant movement (e.g. rotation)between the wiper and the interior lens capsular surface.

Based on mechanics, it is highly desirable that tip portions of thehaptic portions are frosted and/or textured to provide the greatestmoment arm for frictional forces between the haptic portions and thelens capsule to improve the wiping capacity by the movement and/orrotation of the wiper within the lens capsule. Further, both sides andthe edges of the haptics portions are preferably frosted and/or texturedto increase the total surface area that is frosted, and thus increasethe amount of frictional resistance to movement of the wiper.

In the context of a one-piece plate-type IOL according to the presentinvention, a portion of one or both haptic portions can be intentionallycolored. The coloration can render the haptics opaque, or partiallytransmissive (i.e. translucent). The coloration can be used independentof any surface frosting, or in combination therewith. For example, thesame surface portions can be both frosted and colored, or differentportions can be frosted and not colored while other portions are notfrosted, but colored.

The coloration can be utilized to reduce the transmittance of lightthrough the haptic portions, for marking the wiper (e.g. trademarklogos, wiper orientation markings, bar codes, etc.).

Wiping and Absorbing Element

In one preferred embodiment, the accessory is an absorbing member 39made of a piece of an absorbing material, such as bonded celluloseacetate, bonded polyolefin, combinations thereof or equivalent materialwith an absorbing capability. The function is to dry the interior of thelens capsular bag by absorbing and removing liquids, such as irrigationsolution or an agent solution. The absorbing member 39 is movablethrough the lumen, into and out of it and can be separated from the tubeand disposed to be exchanged for a new absorbing piece until the lenscapsule has been dried or liquids have properly been removed.

It can be provided in the form of an elongated stick or pin, preferablyS-shaped, for providing a good sweeping action inside the capsule duringoperation. The diameter of the absorbing member is smaller than theinner diameter of the lumen of the tube, preferably 0.2 to 1.5 mm, suchas 0.5 mm. The diameter of the shaft or the thread to which the stick isattached to, should be smaller than the inner diameter of the lumen,similar as for the stick. The stick and the shaft/thread is preferablyattached to each other by physical or chemical bonding, such as by glue,friction etc.

In one preferred embodiment the absorbing element is made of anexpandable material, such as foam-rubber or foam plastic, bondedcellulose acetate, bonded polyolefin, that is able to be compressed forpassing the leakage preventive tube, and able to be expanded inside thelens capsule for wiping and absorbing solutions inside the capsule.

In one preferred embodiment, the absorbing element is pretreated with anagent solution that can be wiped on the interior surface of the lenscapsule.

A great advantage with the method according to the invention is that itis possible to employ a low dose of agent solution and a smalladministered volume.

The following doses correspond to experimental treatments in rabbits.The principle is applicable in to other species, such as human beings.

In a normal situation, 0.1 to 0.2 ml of the agent solution is needed tofill the capsule completely without the use of a gas expanded capsule.The active agent can be selected from cell killing, or cell passivatingcompounds, such as 5-fluorouracil, doxorubicin, gene modifyingsubstances, saporin just to mention a few possible alternatives.

Additives that enhances the function of the agent solutions are a dye(e.g. Trypan blue, fluorescin) to render the solution easily visible,detergents (e.g. Tween® (polyoxyethylene (20) sorbitan mono-oleate),SDS, saponin) to improve the spreading of the solution inside the lenscapsule over the inner surface thereof.

The volume is dependent on the size of the capsule. This correspond to adose of 10 to 20 mg saponin when administering a solution with a saponinconcentration of 100 mg/ml. Surprisingly, it was found that much lowerdoses, a dose of 1 to 5 mg saponin, is enough to achieve the same resultor even better. This corresponds to 0.01 to 0.05 ml of the agentsolution when administering a solution with a saponin concentration of100 mg/ml. In conclusion, the necessary dose in a gas expanded capsulehas surprisingly been found to be 10 to 50% of the necessary dosewithout the gas. A saponin concentration of 100 mg/ml was found to havegood efficacy in rabbit experiments. Most likely the necessaryconcentration is much lower, but a dose titration curve has not yet beenmade. It seems obvious to find the lowest possible concentration to beused by a dose titration curve. The gain of using a gas expanded capsulewill be similar at even lower concentrations of an active agent, such assaponin.

It is also possible to use other substances in similar proportions asthose illustrated above, and obtain the benefit of the techniqueaccording to the invention, namely to be able to use lower doses overall. Examples of other substances are doxorubicin, 5-flurouracil,saporin.

Furthermore, it was surprisingly found that including a detergent in theagent solution, improved the administration of the solution to the lensepithelial cells. If the capsular surface is dry when administering theagent solution, approximately 0.05 ml is needed to distribute an agentsolution over the entire surface. By combining the solution with adetergent this volume can be reduced to 0.02 ml or less, correspondingto the same reduction in the given dose of the active agent.

The addition of a viscoelastic substance to the agent solution,0.05%-25%, preferably 0.05-5%, suitably 0.05-3%, makes the risk ofleakage less pronounced, and will enable control of the behavior of theagent solutions distribution inside the eye and its lens capsule.

A low concentration of hyaluronic acid, for example, 0.5% hyaluronicacid (based on dilution of Healon (Pharmacia, Sweden), with a MW of 4000 kDa.) slows down the spreading of the agent solution.

A higher concentration of hyaluronic acid, for example, 2.0% hyaluronicacid (based on dilution of Healon5 (Pharmacia, Sweden), with a MW of 4000 kDa.) makes the agent solution very rigid or stiff and can thereforeonly be actively distributed, i.e. spread out at the inner surface ofthe lens capsule with a specially designed device.

Other viscoelastic substances that could be useful are thermo-elasticsubstances (e.g. polyoxyethylene-polyoxypropylene block copolymers; anexample being Lutrol®); and methyl cellulose.

Proposed Composition with Hyaluronic Acid

0.5% hyaluronic acid

0.1% trypan blue

0.5% saponin

hypotonic solution

The solution is applied directly to the inner surface of the lenscapsule, and spread along the surface with a rubbing device. Theequilibrium between the spreading function of the surfactant and thecontrolling function of the viscoelasticum is important for obtainingthe most efficient spread and most effective prevention of leakage outof the capsule.

The small doses and volumes have major advantages from a safety aspect,namely to avoid injuries to delicate tissues of the eye, such as thecorneal endothelium. For example, a small dose is quickly diluted byirrigation solution to a less harmful concentration.

The invention being thus described, it will be obvious that the same maybe varied in many ways. Such variations are not to be regarded as adeparture from the spirit and scope of the invention, and all suchmodifications as would be obvious to one skilled in the art are intendedto be included within the scope of the following claims.

1. A device (10) for preventing leakage of gas from a lens capsule of aneye, to which a capsulorhexis has been made, during manipulationsperformed inside said lens capsule, comprising a tube (12) having aproximal (P) and a distal (D) end, and at least one lumen (14) extendingbetween said ends, said tube (12) being adapted to be located with itsdistal end positioned in the vicinity of said capsulorhexis of the lenscapsule of the eye, and with its proximal end positioned outside the eyeduring said manipulations; at least one barrier member (16; 17) providedwith the tube (12) such that gas that has been introduced into the lenscapsule is prevented to escape therefrom.
 2. The device according toclaim 1, wherein there is provided on the distal end of the tube a thin,flexible flat lid member (20) covering the distal opening of the tube,and having an extension such that once in place inside the lens capsule,it covers and overlaps the capsulorhexis, thereby forming a seal.
 3. Thedevice according to claim 2, wherein the lid member (20) is providedwith a slit.
 4. The device according to claim 1, comprising a pluralityof lumens.
 5. The device according to claim 1, wherein at least onelumen is filled with a visco elastic substance (17), forming a barrieragainst gas leakage.
 6. The device according to claim 1, wherein thedevice is provided with a plurality of barrier members (16).
 7. Thedevice according to claim 1, further comprising a funnel (18) providedat the proximal end of the tube (12).
 8. The device according to claim7, wherein the funnel (18) forms an angle with the tube (12).
 9. Thedevice according to claim 1, wherein the tube (12) is provided with afixation member (22; 28), ascertaining a correct position of the deviceonce placed in its operative position.
 10. An active agent solution forthe treatment of an eye to prevent Posterior Capsular Opacification(PCO), comprising as the active agent a compound selected from cellkilling, or cell passivating compounds; additives that enhance thefunction of the agent solution, selected from a dye to render thesolution easily visible; detergents to improve the spreading of thesolution inside the lens capsule over the inner surface thereof; andsaponin in a concentration of less than 100 mg/ml, preferably less than50 mg/ml, more preferably less than 30 mg/ml.
 11. An active agentsolution according to claim 10, wherein the active agent is selectedfrom saponin, 5-fluorouracil, doxorubicin, gene modifying substances,saporin, SDS, Tween®.
 12. An active agent solution according to claim10, wherein the dye is selected from Trypan blue, fluorescein.
 13. Anactive agent solution according to claim 10, wherein the detergent isselected from Tween®, SDS, saponin.
 14. An active agent solutionaccording to claim 10, further comprising a viscoelastic compound. 15.An active agent solution according to claim 15, wherein the viscoelasticcompound is selected from hyaluronic acid, thermo-elastic substances,and methylcellulose.
 16. An active agent solution according to claim 10,comprising a hypotonic solution.
 17. An active agent solution accordingto claim 10, comprising 0.5% hyaluronic acid, 0.1% trypan blue, 0.5%saponin, and hypotonic solution.
 18. A method of eye surgery, comprisingthe steps of: making an incision to gain access to the interior of aneye; making a capsulorhexis in the lens capsule; removing the lens fromthe lens capsule of an eye; sealing the capsulorhexis with a sealingmeans/device, to vide gas leakage proof sealing; expanding the lenscapsule with a gas; performing a desired operation inside said expandedlens capsule.
 19. The method according to claim 18, wherein the incisionis a scleral or corneal incision.
 20. The method according to claim 18,wherein the lens is removed by phacoemulsification, by irrigation andaspiration or by extra capsular lens extraction (ECLE).
 21. The methodaccording to claim 18, wherein the gas is selected from inert gases,such as air, nitrogen, noble gases.
 22. The method according to claim18, wherein the operation that is performed comprises administering anactive agent for killing and/or passivating any residual epithelialcells.
 23. The method according to claim 18, wherein the operation thatis performed comprises working the inner surface of the lens capsulewith a wiping device to physically release/detach any residualepithelial cells.
 24. The method according to claim 18, wherein theoperation that is performed comprises wiping the inner surface of thelens capsule with a wiper device to dry out any unwanted residualliquids, and/or to spread agent solution over the surface.
 25. Themethod according to claim 24, wherein the wiper device comprisesabsorbent members.